@article {Mozaffari:February 2004:0007-1048:315, author = "Mozaffari F.", author = "Hansson L.", author = "Kiaii S.", author = "Ju X.", author = "Rossmann E.D.", author = "Rabbani H.", author = "Mellstedt H.", author = "Osterborg A.", title = "Signalling molecules and cytokine production in T cells of multiple myeloma-increased abnormalities with advancing stage", journal = "British Journal of Haematology", volume = "124", year = "February 2004", abstract = "Summary

T-cell immune dysfunction in patients with malignant tumours has been attributed to the altered expression of components of the T-cell receptor (TCR)/CD3 complex and their associated intracellular protein tyrosine kinases. In this study, four-colour flow cytometry was applied to study the surface bound molecules TCR, CD28, CD152 and CD154 involved in T-cell signalling and the signal transduction molecules CD3, p56^lck, p59^fyn, ZAP-70 and phosphatidyl-inositol-3 kinase (PI3-k) as well as the intracellular cytokines interferon- (IFN-), interleukin (IL)-4 and IL-2 as a functional read-out of non-stimulated and superantigen (staphylococcus enterotoxin B)-stimulated blood T cells of multiple myeloma (MM) patients at different stages of the disease. Multiple abnormalities were demonstrated in the CD4 and CD8 populations, both under non-stimulated and superantigen-stimulated conditions. There was a marked reduction, particular in advanced stage MM, in the proportion of CD4 and CD8 cells expressing CD28, CD152, CD3, p56^lck, ZAP-70 and PI3-k. The level of intracellular T-cell cytokines (IFN-, IL-2 and IL-4) was normal or increased in non-stimulated cells but activation-induced cytokine production was impaired. These results illustrated profound and multiple T-cell signalling defects, from the surface and down-stream, consistent with involvement of a master T-cell function, especially in advanced stage MM. These data should be taken into consideration when developing immune-based therapeutic approaches and when applying new emerging technologies that aim to restore T-cell functions.", pages = "315-324(10)", url = "http://www.ingentaconnect.com/content/bsc/bjh/2004/00000124/00000003/art00010" doi = "doi:10.1046/j.1365-2141.2003.04789.x" }